An organocatalytic asymmetric Mannich reaction of pyrazoleamides with cyclic trifluoromethyl ketimines: enantioselective access to dihydroquinazolinone skeletons.

Abstract

An organocatalyzed asymmetric Mannich reaction of pyrazoleamides and cyclic trifluoromethyl ketimines with a chiral bifunctional amine-squaramide as the catalyst was developed. A wide range of trifluoromethyl dihydroquinazolinone derivatives bearing adjacent quaternary and tertiary stereogenic centers were readily obtained in good to excellent yields (up to 99%) with high diastereo- and enantioselectivities (up to 99% ee and >20 : 1 dr). The large scale experiment and transformation of the product have also been demonstrated.